Cognition in Essential Tremor: A Neuroimaging and Biomarker Study

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Essential tremor (ET) is among the most prevalent neurological disorders in the world. In addition to the hallmark feature of bilateral kinetic tremor, individuals with essential tremor often present with mild cognitive changes that have been primarily characterized as dysexecutive and viewed as being related to abnormalities in cerebello-cortical networks. However, growing evidence suggests that cognitive difficulties can extend beyond the frontal-executive domain, and epidemiological research has shown that individuals with ET are at an increased risk for developing dementia compared to age-matched peers. Prior research conducted by the applicant identified a subgroup of ET patients who had broader cognitive deficits, including poor memory. This gives rise to the question of whether there may be more widespread neural changes occurring outside cerebellar networks in at least a subset of individuals with ET. Indeed, preliminary findings from neuroimaging and neuropathological studies have suggested that there may be a link between ET and Alzheimer’s disease. Further research is warranted to explore this link, including examining biomarkers associated with cognitive decline. The overall goal of the current study is to better understand the neural correlates of cognition in ET. The proposed study aims to 1) identify cognitive phenotypes in ET using a data-driven (cluster analytic) approach and comprehensive neurocognitive assessment, 2) determine whether different cognitive profiles in ET vary in structural brain changes (i.e., free-water, volume), and 3) to explore whether plasma-acquired biomarkers associated with Alzheimer’s disease are elevated in individuals with ET who have memory-related changes relative to those who do not. Innovative features of the proposed study include determining neuroanatomical correlates of cognition in individuals with ET who have different types of cognitive deficits and use of free-water imaging and plasma biomarkers as sensitive and powerful in vivo markers of early neurodegeneration. Findings from this study may increase current understanding about the nature and heterogeneity of cognitive changes in ET, with the potential to provide further information on the link between ET and dementia. The proposed project will also provide the applicant with additional training beyond that included in her Ph.D. program. Specifically, training goals will include 1) hands-on training in magnetic resonance imaging data processing and analysis with emphasis on structural (T1) and free-water imaging, 2) coursework in neural bases and mechanisms underlying cognitive dysfunction in age-related neurological disorders, 3) didactics in plasma biomarkers associated with Alzheimer’s disease and dementia, 4) training in using programming languages for statistical computing and neuroimaging processing, 5) development of professional and career skills. The applicant is supported by a strong research environment with the necessary resources and infrastructure for completion of the proposed project, as well as a productive mentoring team with specific expertise in the proposed areas of study.